Three prime repair exonuclease 1 preferentially degrades the integration-incompetent HIV-1 DNA through favorable kinetics, thermodynamic, structural, and conformational properties.

ABSTRACT: HIV-1 integration into the human genome is dependent on 3'-processing of the viral DNA. Recently, we reported that the cellular Three Prime Repair Exonuclease 1 (TREX1) enhances HIV-1 integration by degrading the unprocessed viral DNA, while the integration-competent 3'-processed DNA remained resistant. Here, we describe the mechanism by which the 3'-processed HIV-1 DNA resists TREX1-mediated degradation. Our kinetic studies revealed that the rate of cleavage (k_cat) of the 3'-processed DNA was significantly lower (approximately 2-2.5-fold) than the unprocessed HIV-1 DNA by TREX1. The k_cat values of human TREX1 for the processed U5 and U3 DNA substrates were 3.8 s^-1 and 4.5 s^-1, respectively. In contrast, the unprocessed U5 and U3 substrates were

SUBMITTER: Prakash P 

PROVIDER: S-EPMC11259700 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature